title: Testes-specific protease 50 (TSP50) promotes cell proliferation through the activation of the nuclear factor κB (NF-κB) signalling pathway.
abstract: TSP50 (testes-specific protease 50) is a testis-specific expression protein, which is expressed abnormally at high levels in breast cancer tissues. This makes it an attractive molecular marker and a potential target for diagnosis and therapy; however, the biological function of TSP50 is still unclear. In the present study, we show that overexpression of TSP50 in CHO (Chinese-hamster ovary) cells markedly increased cell proliferation and colony formation. Mechanistic studies have revealed that TSP50 can enhance the level of TNFα (tumour necrosis factor α)- and PMA-induced NF-κB (nuclear factor κB)-responsive reporter activity, IκB (inhibitor of NF-κB) α degradation and p65 nuclear translocation. In addition, the knockdown of endogenous TSP50 in MDA-MB-231 cells greatly inhibited NF-κB activity. Co-immunoprecipitation studies demonstrated an interaction of TSP50 with the NF-κB-IκBα complex, but not with the IKK (IκB kinase) α/β-IKKγ complex, which suggested that TSP50, as a novel type of protease, promoted the degradation of IκBα proteins by binding to the NF-κB-IκBα complex. Our results also revealed that TSP50 can enhance the expression of NF-κB target genes involved in cell proliferation. Furthermore, overexpression of a dominant-negative IκB mutant that is resistant to proteasome-mediated degradation significantly reversed TSP50-induced cell proliferation, colony formation and tumour formation in nude mice. Taken together, the results of the present study suggest that TSP50 promotes cell proliferation, at least partially, through activation of the NF-κB signalling pathway.
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Zhen-Bo
authors.initials: ZB
authors.lastname: Song
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Bao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xu-Guang
authors.initials: XG
authors.lastname: Mi
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Yu
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zheng
authors.forename: Yan-Xin
authors.initials: YX
authors.lastname: Huang
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Li
mesh_terms: D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D012697:Serine Endopeptidases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D016328:NF-kappa B; D012697:Serine Endopeptidases; C446379:testis-specific protease 50